麦考酚酸肠肝循环药动学模型的建立  

Pharmacokinetic model for the enterohepatic circulation of mycophenolic acid

作　　者：焦正[1] 沈杰[1] 仲珑瑾[1] 郁韵秋[2] 钟明康[1] 

机构地区：[1]复旦大学附属华山医院临床药学研究室,上海200040 [2]复旦大学药学院,上海200032

出　　处：《药学学报》2006年第3期272-276,共5页Acta Pharmaceutica Sinica

基　　金：上海市自然科学基金资助项目(03ZR14010);上海市卫生局百人计划II期资助项目(98BR009).

摘　　要：目的建立麦考酚酸肠肝循环的药动学模型。方法20名健康志愿者单剂量口服吗替麦考酚酯500mg,在服药前及服药后48 h内的不同时间点取血。HPLC法测定血药浓度。非线性混合效应模型进行模型拟合和参数计算。结果麦考酚酸肠肝循环模型包括一肠道室、一胆囊室和一中央室。模型对于血药浓度的经时过程和主要药动学参数AUC0-t,Cm ax和Tm ax预测效果良好。结论模型具有代表性,可为进一步的临床研究奠定基础。Aim To develop a pharmacokinetic model for the enterohepatic circulation of mycophenolic acid （MPA）. Methods Twenty healthy volunteers were orally given a single dose of 500 mg mycophenolate mofetil. Plasma samples were collected during 48 hours and MPA concentration was measured by HPLC method. Pharmacokinetic （PK） model was established based on physiological and biopharmaceutical consideration and PK parameters were obtained using nonlinear mixed effect model. Results The proposed model included an intestinal compartment and gall bladder compartment in addition to the central compartment. The predicted time-concentration curve and AUC0-t C Tmax estimated by the established model were in agreement with the observations. Conclusion The established model was well defined for the MPA disposition and could afford a useful approach for the further clinical investigation.

关 键 词：麦考酚酸 肠肝循环 非线性混合效应模型 

分 类 号：R969.1[医药卫生—药理学]